Single-use sterile bag systems were introduced to the market in 1986. Initially, bags were used to replace glass carboys and as disposable shipping containers for media and buffers used for cell cultivation. The advantage of single-use vessels is elimination of cross-contamination, which is a major problem with stainless steel and glass containers that must be cleaned and sterilized between usages. The trends toward utilization of single-use agitation systems have increased over the past several years. Several agitation modalities have been developed for single-use applications including recirculation loops, rocking, and integral impeller techniques, but there are limitations with all of these methods. Vibrational agitation systems have been in existence for more than 40 years but sparingly utilized in pharmaceutical and biotechnology applications over concerns about cross contamination due to integrity in the shaft sealing designs. There have been recent attempts at deploying vibrating disk methods in disposable bags and some have proven successful but they require mechanical coupling of the shaft to the bag surface. This technique has limitations, in that it only enables the use of vibrating agitation in bags and is difficult to scale down. The vibrating disk technique has proven to be effective in a wide range of vessels and vessel volumes. Additionally, there has been an increase in the use of continuous bioprocessing including, sampling, harvesting, and perfusion which has been shown to result in membrane clogging when standard, lateral flow filtration techniques are employed without the inclusion of agitation or lateral flow. The sampling device facilitates the retention of cells while removing product, cellular debris, spent media, and other waste products. Other sampling devices either fail due to clogging, are too complex, cumbersome, or costly to operate and maintain.
The present invention addresses these various shortcomings in the art by providing a hermetically sealed housing which does not require mechanical coupling of the shaft or agitator to the actuator. The actuator can be applied to single-use (disposable) or re-useable equipment. It can be used with flexible containers (bags, etc.) or rigid vessels (plastic, glass, metal, etc.), and is scalable from microliter to kiloliter volumes. The apparatus can be used for mixing, agitating (i.e., foam breaking), separation, continuous sampling and/or harvesting (filtration), gas mixing, and various other applications. The agitation devices can be various mixing devices, screens, scaffolds, matrices, pistons, plungers, or any other device to meet specific agitation requirements. The actuator housing can be integral to the vessel or detachable.